Natural killer T (NKT) cells represent a novel cell lineage characterized by the restricted expression of an invariant TCRα chain encoded by Vα24/JαQ gene segments in humans and Vα14/Jα281 + in mice. Different aspects of the immune response are severely affected by age. Thus, we have studied the effect of aging on NKT cells from healthy elderly individuals. Our results demonstrated a decreased percentage of CD3 + Vα24 + cells in peripheral blood from elderly donors, whereas mainstream T lymphocytes showed an age-associated decrease in the expression of CD28, the vast majority of CD3 + Vα24 + cells from old individuals were CD28 + . A significant increase in the percentage of Vα24 + cells with the CD4 - CD8 + phenotype was also found in the elderly, indicating a redistribution of Vα24 + subsets according to the CD4/CD8 phenotype. Given the important immunoregulatory role of these cells, the decrease of NKT cells will contribute to the deleterious immune response in the elderly.